Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV

Won Jun Lee; Haoxiang Cheng; Bridget M Whitney; Robin M Nance; Sierra R Britton; Kristina Jordahl; Sara Lindstrom; Stephanie A Ruderman; Mari M Kitahata; Michael S Saag; Amanda L Willig; Greer Burkholder; Joseph J Eron; Jason C Kovacic; Johan L M Björkegren; W Christopher Mathews; Edward Cachay; Matthew J Feinstein; Mathew Budoff; Peter W Hunt; Richard D Moore; Jeanne Keruly; Mary E McCaul; Geetanjali Chander; Allison Webel; Kenneth H Mayer; Joseph A Delaney; Paul K Crane; Claudia Martinez; Heidi M Crane; Ke Hao; Inga Peter

doi:10.1016/j.ijcard.2023.04.058

Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV

Int J Cardiol. 2023 Jul 15:383:15-23. doi: 10.1016/j.ijcard.2023.04.058. Epub 2023 May 4.

Authors

Won Jun Lee¹, Haoxiang Cheng¹, Bridget M Whitney², Robin M Nance², Sierra R Britton³, Kristina Jordahl⁴, Sara Lindstrom⁴, Stephanie A Ruderman⁴, Mari M Kitahata², Michael S Saag⁵, Amanda L Willig⁵, Greer Burkholder⁵, Joseph J Eron⁶, Jason C Kovacic⁷, Johan L M Björkegren⁸, W Christopher Mathews⁹, Edward Cachay⁹, Matthew J Feinstein¹⁰, Mathew Budoff¹¹, Peter W Hunt¹², Richard D Moore¹³, Jeanne Keruly¹³, Mary E McCaul¹³, Geetanjali Chander¹⁴, Allison Webel¹⁵, Kenneth H Mayer¹⁶, Joseph A Delaney¹⁷, Paul K Crane², Claudia Martinez¹⁸, Heidi M Crane², Ke Hao¹, Inga Peter¹⁹

Affiliations

¹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, New York, USA.
² Department of Medicine, University of Washington School of Public Health, Seattle, WA, USA.
³ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, New York, USA; Department of Population Health Sciences, Weill Cornell Medical College of Cornell University, New York, NY, USA.
⁴ Department of Epidemiology, University of Washington School of Medicine, Seattle, WA, USA.
⁵ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA; Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St Vincent's Clinical School, University of NSW, Australia.
⁸ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, New York, USA; Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
⁹ Department of Medicine, University of California San Diego, San Diego, CA, USA.
¹⁰ Department of Medicine, Northwestern University Feinberg School of Medicine, Evanston, IL, USA.
¹¹ Deparment of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹² Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
¹³ Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹⁴ Department of Medicine, University of Washington School of Public Health, Seattle, WA, USA; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹⁵ Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; School of Nursing, University of Washington, Seattle, WA, USA.
¹⁶ The Fenway Institute at Fenway Health, Boston, MA, USA.
¹⁷ Department of Medicine, University of Washington School of Public Health, Seattle, WA, USA; College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Canada.
¹⁸ Department of Medicine, Division of Cardiology, University of Miami Miller School of Medicine, Florida, USA.
¹⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, New York, USA. Electronic address: inga.peter@mssm.edu.

PMID: 37149004
PMCID: PMC10247524 (available on 2024-07-15)
DOI: 10.1016/j.ijcard.2023.04.058

Abstract

Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH.

Methods: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI.

Results: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption.

Conclusions: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

Keywords: Energy metabolism; HIV; Polygenic risk score; Type 1 myocardial infarction; Type 2 myocardial infarction.

MeSH terms

Anterior Wall Myocardial Infarction* / complications
HIV Infections* / epidemiology
HIV Infections* / genetics
Humans
Myocardial Infarction* / diagnosis
Myocardial Infarction* / genetics
Myocardium
Risk Factors

Abstract

MeSH terms

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